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Cushing's syndrome clinical features buffalo hump moon face

This clinical photograph shows a pediatric patient presenting with characteristic physical features of Cushing syndrome. The face exhibits a rounded, 'moon facies' appearance with associated submental fat deposition (double chin). There is evidence of central adiposity with a protuberant abdomen and fullness in the supraclavicular and upper chest regions, consistent with truncal obesity. A visible dorsocervical fat pad, or 'buffalo hump', is present at the base of the neck. On the patient's left flank, a linear surgical scar is visible, indicating a prior operative intervention. These findings are visually representative of hypercortisolism, which in this case is associated with an ACTH-secreting ganglioneuroma. The image serves as an educational example for identifying the systemic manifestations of glucocorticoid excess in children.

This clinical photograph shows a pediatric patient presenting with characteristic physical features of Cushing syndrome. The face exhibits a rounded, 'moon facies' appearance with associated submental fat deposition (double chin). There is evidence of central adiposity with a protuberant abdomen and fullness in the supraclavicular and upper chest regions, consistent with truncal obesity. A visible dorsocervical fat pad, or 'buffalo hump', is present at the base of the neck. On the patient's left flank, a linear surgical scar is visible, indicating a prior operative intervention. These findings are visually representative of hypercortisolism, which in this case is associated with an ACTH-secreting ganglioneuroma. The image serves as an educational example for identifying the systemic manifestations of glucocorticoid excess in children.

A composite of five clinical photographs illustrating the classic physical manifestations of Cushing's syndrome in a 26-year-old female. The top-left image shows a frontal view of the face, demonstrating a 'moon face' appearance characterized by a rounded facial contour and prominent, plethoric (flushed) cheeks. The top-center photograph displays the posterior cervical and upper thoracic region, showing a significant dorsocervical fat pad, commonly referred to as a 'buffalo hump.' The remaining three images (top-right, bottom-left, and bottom-right) focus on the patient's trunk and limbs, revealing wide, violaceous (purplish) striae distensae across the abdomen and thighs. These striae appear as deep, linear streaks indicating thinning of the dermis. Collectively, these visual findings are hallmark cutaneous and structural signs of chronic hypercortisolism, which in this clinical context was secondary to a left adrenal adenoma. The images serve as educational references for endocrinology and dermatology, highlighting the systemic physical changes associated with cortisol excess.

A composite of five clinical photographs illustrating the classic physical manifestations of Cushing's syndrome in a 26-year-old female. The top-left image shows a frontal view of the face, demonstrating a 'moon face' appearance characterized by a rounded facial contour and prominent, plethoric (flushed) cheeks. The top-center photograph displays the posterior cervical and upper thoracic region, showing a significant dorsocervical fat pad, commonly referred to as a 'buffalo hump.' The remaining three images (top-right, bottom-left, and bottom-right) focus on the patient's trunk and limbs, revealing wide, violaceous (purplish) striae distensae across the abdomen and thighs. These striae appear as deep, linear streaks indicating thinning of the dermis. Collectively, these visual findings are hallmark cutaneous and structural signs of chronic hypercortisolism, which in this clinical context was secondary to a left adrenal adenoma. The images serve as educational references for endocrinology and dermatology, highlighting the systemic physical changes associated with cortisol excess.

A composite of three clinical photographs demonstrating classic Cushingoid features in a pediatric patient. Panel A: Close-up of the face showing 'moon facies' characterized by rounded cheeks and noticeable facial plethora (erythema). Panel B: View of the left lower extremity showing multiple wide, slightly depressed, erythematous-to-violaceous striae (skin stretch marks) distributed across the proximal thigh and distal leg. Panel C: Lateral view of the upper back and neck region showing a prominent dorsocervical fat pad (buffalo hump) accompanied by significant hypertrichosis (increased hair growth). These visual markers are key clinical indicators of Cushing syndrome, whether endogenous or iatrogenic. The image provides educational value for medical students and clinicians in identifying dermatological and morphological manifestations of hypercortisolism.

A composite of three clinical photographs demonstrating classic Cushingoid features in a pediatric patient. Panel A: Close-up of the face showing 'moon facies' characterized by rounded cheeks and noticeable facial plethora (erythema). Panel B: View of the left lower extremity showing multiple wide, slightly depressed, erythematous-to-violaceous striae (skin stretch marks) distributed across the proximal thigh and distal leg. Panel C: Lateral view of the upper back and neck region showing a prominent dorsocervical fat pad (buffalo hump) accompanied by significant hypertrichosis (increased hair growth). These visual markers are key clinical indicators of Cushing syndrome, whether endogenous or iatrogenic. The image provides educational value for medical students and clinicians in identifying dermatological and morphological manifestations of hypercortisolism.

A composite of four clinical photographs demonstrating the classic physical manifestations of Cushing's syndrome. Image (a) is a frontal view of the face showing 'moon facies' characterized by facial rounding and plethora. Image (b) provides a lateral view of the upper back and neck, highlighting a prominent dorsocervical fat pad (buffalo hump). Image (c) shows a profile of the torso, illustrating centripetal obesity and wide, purplish striae distensae along the abdomen and flanks. Image (d) is a close-up of the fingernails, displaying hyperpigmentation and longitudinal ridging, which may suggest associated adrenocorticotropic hormone (ACTH) excess. The collection serves as an educational reference for medical students to identify systemic signs of hypercortisolism, including skin atrophy and telangiectasias.

A composite of four clinical photographs demonstrating the classic physical manifestations of Cushing's syndrome. Image (a) is a frontal view of the face showing 'moon facies' characterized by facial rounding and plethora. Image (b) provides a lateral view of the upper back and neck, highlighting a prominent dorsocervical fat pad (buffalo hump). Image (c) shows a profile of the torso, illustrating centripetal obesity and wide, purplish striae distensae along the abdomen and flanks. Image (d) is a close-up of the fingernails, displaying hyperpigmentation and longitudinal ridging, which may suggest associated adrenocorticotropic hormone (ACTH) excess. The collection serves as an educational reference for medical students to identify systemic signs of hypercortisolism, including skin atrophy and telangiectasias.

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Cushing syndrome diagnosis treatment

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Cushing's Syndrome: A Comprehensive Overview

Definition

Cushing's syndrome is a clinical condition resulting from prolonged, inappropriately elevated exposure of tissues to glucocorticoids (cortisol excess - hypercortisolism). It is rare, occurring in 2-5 per million people per year, though up to 8 per 100,000 persons may have it when subclinical cases are included. The median age of diagnosis is 40 years, with a 3:1 female-to-male predominance.
"Cushing disease" specifically refers to hypercortisolism caused by an ACTH-secreting pituitary adenoma. "Cushing syndrome" is the broader term encompassing all causes.

Pathophysiology and the HPA Axis

The zona fasciculata of the adrenal cortex secretes up to 20 mg of cortisol daily, regulated through the hypothalamic-pituitary-adrenal (HPA) axis:
  1. The hypothalamus releases CRH (corticotropin-releasing hormone) - driven by stress, circadian rhythm, and low serum cortisol.
  2. CRH stimulates the anterior pituitary's corticotropic cells to secrete ACTH (cleaved from the pro-opiomelanocortin [POMC] precursor).
  3. ACTH drives the adrenal cortex to produce cortisol.
  4. Cortisol exerts negative feedback on both the hypothalamus and pituitary, suppressing CRH and ACTH.
CRH follows tight circadian patterning. Cortisol peaks in the early morning and reaches its nadir around 11 PM. Even small disruptions in this rhythm are pathologic.
HPA axis diagram showing Cushing's syndrome pathophysiology
Left: Pituitary adenoma (Cushing disease) - elevated ACTH, bilateral adrenal hyperplasia, elevated cortisol. Center: Ectopic ACTH-producing tumor - elevated ACTH, bilateral adrenal stimulation, elevated cortisol. Right: Adrenal adenoma (ACTH-independent) - suppressed ACTH, one adrenal with tumor, elevated cortisol.

Classification / Causes

1. Exogenous (Iatrogenic) - MOST COMMON

  • Chronic use of exogenous corticosteroids (systemic, topical, inhaled, nasal, conjunctival)
  • Serum cortisol is low (adrenal cortex is suppressed)
  • Especially common in children with topical applications

2. ACTH-Dependent (~80% of endogenous cases)

SubtypeDetails% of Endogenous
Cushing disease (pituitary adenoma)Microadenoma secreting ACTH; bilateral adrenal hyperplasia~68%
Ectopic ACTH syndromeACTH secreted by non-pituitary tumors (small cell lung cancer, carcinoid, pheochromocytoma, MEN2A)~12%
Ectopic CRH secretionRare; CRH-producing tumors stimulate pituitaryRare

3. ACTH-Independent (~20% of endogenous cases)

SubtypeDetails
Adrenal adenomaUnilateral, benign; autonomous cortisol production; contralateral adrenal atrophies
Adrenal carcinomaOften large, unilateral, aggressive
Bilateral adrenal hyperplasiaIncludes PPNAD (Primary Pigmented Nodular Adrenocortical Disease) - seen in 30% of Carney complex
McCune-Albright syndromeRare association
MEN type IRare feature

4. Pseudo-Cushing Syndrome

HPA overactivity mimicking Cushing's but without true disease. Seen in depression, anxiety disorders, alcoholism, poorly controlled diabetes, and morbid obesity.

Clinical Features

The manifestations stem from the anabolic and anti-anabolic effects of glucocorticoid excess.

Central / Fat Redistribution

  • Moon facies - rounded face from fat deposition
  • Buffalo hump (dorsocervical fat pad) - fat deposition at the back of the neck/upper thoracic region
  • Central/truncal obesity - with sparing of the limbs
  • Supraclavicular fat pads
  • Submental fat deposition ("double chin")

Skin (Dermatologic Signs - highly characteristic)

  • Wide, violaceous (purple) striae - abdomen, buttocks, breasts, upper arms, thighs (>1 cm wide, purplish; unlike pale stretch marks of obesity)
  • Skin thinning and fragility - "cigarette paper" wrinkling
  • Easy bruising / ecchymoses
  • Plethora - reddish flush of the cheeks, anterior neck, and V of the chest
  • Hypertrichosis - facial lanugo in women
  • Acne
  • Poor wound healing
  • Susceptibility to superficial fungal infections (dermatophyte, Pityrosporum)
  • Liddle sign - skin peels off easily when adhesive tape is removed
  • Occasionally: livedo reticularis, purpura, poikiloderma-like changes

Musculoskeletal

  • Proximal muscle weakness (myopathy) - difficulty rising from a chair
  • Osteoporosis - vertebral fractures, kyphosis, back pain
  • Loss of height

Cardiovascular / Metabolic

  • Hypertension (very common, due to mineralocorticoid effects of cortisol)
  • Generalized arteriosclerosis
  • Hyperglycemia / diabetes mellitus - in ~20% of patients
  • Hypokalemia
  • Dyslipidemia

Endocrine / Reproductive

  • Hirsutism and oligomenorrhea/amenorrhea in women (androgen co-secretion)
  • Loss of libido in men and women
  • Hypogonadotropic hypogonadism

Neuropsychiatric

  • Depression, anxiety, emotional lability
  • Psychosis (in severe cases)
  • Cognitive impairment

Other

  • Hyperpigmentation - only in ACTH-dependent causes (excess ACTH stimulates melanocortin receptors); especially noticeable on knuckles, oral mucosa, scars
  • Polycythemia
  • Urolithiasis (nephrolithiasis)
  • Immunosuppression
Here are classic clinical photographs showing the hallmark features:
Classic Cushing's syndrome features: moon facies, buffalo hump, violaceous striae
Moon facies, buffalo hump, and wide violaceous striae in a 26-year-old female with left adrenal adenoma.
Pediatric Cushing's syndrome with moon facies and buffalo hump
Pediatric Cushing's syndrome: moon facies, central adiposity, buffalo hump, and surgical scar.

Distinguishing Cushing's Syndrome from Simple Obesity

Since metabolic syndrome/obesity shares anabolic features (fat deposition, hypertension, glucose intolerance), focus on the anti-anabolic signs of cortisol excess which are NOT seen in simple obesity:
  • Wide purple striae (>1 cm)
  • Proximal muscle weakness
  • Skin thinning and easy bruising
  • Unexplained osteoporosis in a young person

Diagnosis

Diagnosis is a two-phase process: screening then confirmation + localization.

Phase 1 - Screening (choose one of three)

TestPrincipleSensitivityNotes
24-hour urinary free cortisol (UFC)Direct measure of free bioavailable cortisol; integrated over 24h~95%Values >4× upper limit of normal are diagnostic; unreliable in GFR <30 mL/min; may miss subclinical disease
Overnight low-dose dexamethasone suppression test (DST)1 mg dexamethasone at 11 PM; measure serum cortisol at 8 AM~95%Failure to suppress cortisol to <50 nmol/L (1.8 μg/dL) = positive. Preferred for incidentaloma workup
Late-night salivary cortisol (LNSC)Cortisol nadir is lost in Cushing's; persistent evening elevationHighPractical outpatient test; reflects free cortisol
Three laboratory hallmarks: (1) elevated cortisol (serum, UFC, or LNSC), (2) loss of circadian rhythm of ACTH/cortisol, and (3) failure to suppress cortisol with low-dose dexamethasone.
Tests that have fallen out of favor: random serum cortisol, plasma ACTH, urinary 17-ketosteroids, insulin tolerance test, loperamide testing.

Phase 2 - Confirming Hypercortisolism (if borderline or high suspicion)

  • 2-day low-dose DST (48-hour, 0.5 mg q6h dexamethasone)
  • Midnight plasma cortisol (in-hospital; >207 nmol/L is diagnostic)

Phase 3 - Localizing the Source

Once hypercortisolism is confirmed:
Step A: Plasma ACTH level
  • ACTH suppressed (<5 pg/mL) → ACTH-independent (adrenal source) → CT/MRI of adrenal glands
  • ACTH elevated or normal (>15 pg/mL) → ACTH-dependent → need further testing
Step B (if ACTH-dependent): High-dose DST
  • Pituitary Cushing disease: cortisol suppresses by >50% (pituitary adenoma retains some sensitivity to very high-dose dexamethasone)
  • Ectopic ACTH: cortisol does NOT suppress
Step C: Imaging
  • Pituitary MRI with gadolinium for pituitary adenoma (may be small; up to 40% are microadenomas invisible on MRI)
  • CT/MRI adrenals for adrenal lesions
  • CRH stimulation test and inferior petrosal sinus sampling (IPSS) for equivocal cases - IPSS is the gold standard for confirming pituitary origin and lateralizing the adenoma

Management

Treatment depends on the underlying etiology.

Cushing Disease (Pituitary Adenoma)

  • First-line: Transsphenoidal surgery (TSS) - resection of the pituitary adenoma; remission rates 65-90%
  • If surgery fails or recurs: repeat TSS, pituitary radiotherapy (stereotactic radiosurgery), bilateral adrenalectomy
  • Nelson's syndrome: occurs after bilateral adrenalectomy when the pituitary adenoma grows aggressively due to loss of cortisol feedback (treated with radiosurgery - recent systematic review PMID 40884684)

Adrenal Adenoma (ACTH-independent)

  • Unilateral adrenalectomy (laparoscopic preferred)
  • Preoperatively: control of hypertension, diabetes, electrolytes
  • Metyrapone (inhibits glucocorticoid synthesis) if severe symptoms need rapid control
  • Critical: postoperative cortisol replacement is mandatory because the contralateral adrenal is suppressed; HPA axis recovery can take 6-24 months

Adrenal Carcinoma

  • Open adrenalectomy (for large tumors)
  • Mitotane (adrenocortical cytotoxic agent) - adjuvant therapy
  • Consent for adjacent organ removal if needed

Ectopic ACTH Syndrome

  • Treat the underlying tumor (resect if possible)
  • If unresectable: bilateral adrenalectomy or medical adrenalectomy
  • Medical therapy options: metyrapone, ketoconazole, mifepristone

Iatrogenic Cushing's

  • Gradual tapering of exogenous corticosteroids (never abrupt discontinuation - risk of adrenal crisis)

Medical Therapy (for all types, especially pre-surgery or inoperable cases)

DrugMechanism
MetyraponeInhibits 11β-hydroxylase → blocks cortisol synthesis
KetoconazoleInhibits multiple steroidogenic enzymes
MifepristoneGlucocorticoid receptor antagonist
MitotaneAdrenocortical cytotoxin; used for carcinoma
PasireotideSomatostatin analogue; reduces ACTH from pituitary
CabergolineDopamine agonist; reduces ACTH in some pituitary tumors

Perioperative Considerations

  • Stress-dose steroids intraoperatively and for 24h post-op
  • VTE prophylaxis (high thrombotic risk due to hypercoagulable state)
  • Antibiotics
  • Cardiopulmonary workup
  • Management of diabetes and hypertension
  • Monitoring for adrenal insufficiency postoperatively

Special Associations

ConditionNotes
Carney complexPrimary Pigmented Nodular Adrenocortical Disease (PPNAD) in 30%
MEN1Rare feature
McCune-AlbrightRare feature
MEN2ARare ectopic Cushing's syndrome via ACTH-secreting medullary thyroid carcinoma or pheochromocytoma
Pseudo-CushingAlcohol abuse can perfectly mimic Cushing's clinically

Key Points Summary

  • Cushing's syndrome = chronic cortisol excess from any cause
  • Most common cause overall = iatrogenic (exogenous steroids)
  • Most common endogenous cause = Cushing disease (pituitary ACTH-secreting adenoma, ~68%)
  • Hyperpigmentation only occurs in ACTH-dependent types
  • Classic discriminatory features: wide purple striae, proximal myopathy, easy bruising, thin skin, unexplained osteoporosis
  • Diagnosis requires biochemical confirmation + source localization
  • The three screening tests are 24-hr UFC, overnight DST, and late-night salivary cortisol
  • Definitive treatment is surgical in most cases
  • Adrenal suppression after cure requires steroid replacement during recovery
Sources: Campbell Walsh Wein Urology, Andrews' Diseases of the Skin, Textbook of Family Medicine 9e, Henry's Clinical Diagnosis and Management by Laboratory Methods, Tietz Textbook of Laboratory Medicine 7e, Frameworks for Internal Medicine, Lippincott Illustrated Reviews Pharmacology, Kaplan & Sadock's Comprehensive Textbook of Psychiatry.
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